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What interventions reduce the risk of contrast nephropathy for high-risk patients?
Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).
Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).
Evidence summary
Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.
A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.
Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.
A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.
TABLE 1
Risk factors for the development of contrast nephropathy
| Advanced age |
| Diabetes mellitus |
| Chronic renal insufficiency |
| Congestive heart failure |
| Acute myocardial infarction |
| Cardiogenic shock |
| Renal transplant |
| Hemodynamic instability |
| Dehydration |
| Low serum albumin |
| Angiotensin-converting enzyme use |
| Nonsteroidal anti-inflammatory drug use |
| Furosemide use |
| Higher volume of contrast media |
| Source: Nikolsky et al, Rev Cardiovasc Med 2003.1 |
TABLE 2
Interventions to reduce risk of contrast nephropathy
| INTERVENTION | SOR | PROTOCOLS |
|---|---|---|
| Acetylcysteine (oral) | A | Acetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6 |
| Hypo-osmolar contrast media | A | A variety of protocols have been demonstrated to be effective.4 |
| Acetylcysteine (IV) | B | 150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7 |
| Iso-osmolar contast media | B | Varying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5 |
| Sodium bicarbonate | B | Patients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2 |
| Isotonic saline | B | 0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3 |
| Hemofiltration | B | Hemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8 |
| SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381. | ||
Recommendations from others
The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10
Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago
The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.
Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.
Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.
1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.
2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.
3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.
4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.
5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.
6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.
7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.
8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.
9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).
10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.
Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).
Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).
Evidence summary
Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.
A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.
Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.
A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.
TABLE 1
Risk factors for the development of contrast nephropathy
| Advanced age |
| Diabetes mellitus |
| Chronic renal insufficiency |
| Congestive heart failure |
| Acute myocardial infarction |
| Cardiogenic shock |
| Renal transplant |
| Hemodynamic instability |
| Dehydration |
| Low serum albumin |
| Angiotensin-converting enzyme use |
| Nonsteroidal anti-inflammatory drug use |
| Furosemide use |
| Higher volume of contrast media |
| Source: Nikolsky et al, Rev Cardiovasc Med 2003.1 |
TABLE 2
Interventions to reduce risk of contrast nephropathy
| INTERVENTION | SOR | PROTOCOLS |
|---|---|---|
| Acetylcysteine (oral) | A | Acetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6 |
| Hypo-osmolar contrast media | A | A variety of protocols have been demonstrated to be effective.4 |
| Acetylcysteine (IV) | B | 150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7 |
| Iso-osmolar contast media | B | Varying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5 |
| Sodium bicarbonate | B | Patients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2 |
| Isotonic saline | B | 0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3 |
| Hemofiltration | B | Hemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8 |
| SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381. | ||
Recommendations from others
The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10
Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago
The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.
Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.
Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.
Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).
Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).
Evidence summary
Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.
A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.
Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.
A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.
TABLE 1
Risk factors for the development of contrast nephropathy
| Advanced age |
| Diabetes mellitus |
| Chronic renal insufficiency |
| Congestive heart failure |
| Acute myocardial infarction |
| Cardiogenic shock |
| Renal transplant |
| Hemodynamic instability |
| Dehydration |
| Low serum albumin |
| Angiotensin-converting enzyme use |
| Nonsteroidal anti-inflammatory drug use |
| Furosemide use |
| Higher volume of contrast media |
| Source: Nikolsky et al, Rev Cardiovasc Med 2003.1 |
TABLE 2
Interventions to reduce risk of contrast nephropathy
| INTERVENTION | SOR | PROTOCOLS |
|---|---|---|
| Acetylcysteine (oral) | A | Acetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6 |
| Hypo-osmolar contrast media | A | A variety of protocols have been demonstrated to be effective.4 |
| Acetylcysteine (IV) | B | 150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7 |
| Iso-osmolar contast media | B | Varying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5 |
| Sodium bicarbonate | B | Patients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2 |
| Isotonic saline | B | 0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3 |
| Hemofiltration | B | Hemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8 |
| SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381. | ||
Recommendations from others
The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10
Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago
The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.
Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.
Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.
1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.
2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.
3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.
4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.
5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.
6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.
7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.
8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.
9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).
10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.
1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.
2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.
3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.
4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.
5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.
6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.
7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.
8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.
9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).
10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.
Evidence-based answers from the Family Physicians Inquiries Network
The impact of stress urinary incontinence on sexual activity in women
Cost-effective management for nephrolithiasis
For patients with first-time kidney stones, conservative therapy (dietary modification only) is the most cost-effective strategy. In recurrent stone formers, both empiric therapy (dietary modification and potassium citrate) and a modified simple metabolic evaluation (one 24-hour urine collection for renal stone risk factors, with both potassium citrate and hydrochlorothiazide for patients with hypercalciuria and potassium citrate alone for patients with normocalciuria) are equally cost-effective. (LOE=2b)
For patients with first-time kidney stones, conservative therapy (dietary modification only) is the most cost-effective strategy. In recurrent stone formers, both empiric therapy (dietary modification and potassium citrate) and a modified simple metabolic evaluation (one 24-hour urine collection for renal stone risk factors, with both potassium citrate and hydrochlorothiazide for patients with hypercalciuria and potassium citrate alone for patients with normocalciuria) are equally cost-effective. (LOE=2b)
For patients with first-time kidney stones, conservative therapy (dietary modification only) is the most cost-effective strategy. In recurrent stone formers, both empiric therapy (dietary modification and potassium citrate) and a modified simple metabolic evaluation (one 24-hour urine collection for renal stone risk factors, with both potassium citrate and hydrochlorothiazide for patients with hypercalciuria and potassium citrate alone for patients with normocalciuria) are equally cost-effective. (LOE=2b)
Overactive bladder: Evaluation and management in primary care
Milk-Alkali Syndrome [published correction appears in: Fed Pract. 2005;22(3):66.]
Three rheumatologic emergencies: A sore toe, a cough, hypertension
How effective is prophylactic therapy for gout in people with prior attacks?
Colchicine (strength of recommendation [SOR]: B, based on 1 double-blind crossover study), allopurinol (SOR: B, based on 2 cohort studies), and weight loss (SOR: B, based on 1 small cohort study) have been shown to reduce symptomatic recurrences of gout, although the data to support their use is limited. Some evidence suggests that despite their serum uric acid–lowering effects, uricosurics (such as probenecid) fail to reduce gout attacks (SOR: B, based on 2 cohort studies). We were unable to find any double-blind, placebo-controlled long-term outcome studies addressing this problem.
Evidence summary
The majority of gout sufferers are uric acid undersecretors rather than overproducers; however, many patients will have a combination of these 2 processes, as well as caloric or purine overindulgence. Efforts to limit the frequency and intensity of gout attacks have focused on reducing the uric acid load or reducing the inflammatory response to intra-articular crystal deposition. Pharmacologic therapies include 1) uricosurics, such as probenecid, sulfinpyrazone and benzbromarone (used mostly in Europe), which increase the renal clearance of uric acid, 2) xanthine oxidase inhibitors such as allopurinol, which limit the formation of uric acid to yield a more water soluble chemical, and 3) anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. Obesity and insulin resistance are associated with elevated uric acid, suggesting that weight loss may also help reduce episodes of gout.
A double-blinded crossover study of 38 veteran men with recurrent gout found that the addition of daily colchicine to uricosurics reduced the frequency of attacks by nearly two thirds in 6 months of follow-up.1 A cohort study of 208 men with confirmed gout who used either daily colchicine alone or colchicine with uricosurics for 2 to 10 years found marked improvements in attack frequency in both groups, yet there was no difference between the intervention groups.2 An additional study followed 734 patients (including some of the subjects in the first cohort study) and reported similar outcomes.3
Allopurinol was studied in 46 patients using prophylactic colchicine with an average follow-up of 12 months.4 Attack rates were unchanged for the first several weeks followed by a decline in the attack rate and a regression of tophi. When allopurinol was added to uricosurics in 48 patients, tophi were reduced.5
An average weight loss of 7.7 kg had a beneficial effect on serum uric acid levels and gout attack rates in 13 nondiabetic men, who were placed on a carefully controlled 1600-calorie diet with 40% of calories from complex carbohydrates.6
In a small study, the addition of uricosurics did not reduce the gout attack rate in 14 patients with nontophaceous gout.7 Patients were followed over 12 to 15 months in a crossover study of colchicine and placebo versus colchicine and sulfinpyrazone. Although this study had limited power, a larger cohort study had similar findings over a longer follow-up period.3
We were unable to find any applicable studies of daily NSAID use, dietary purine control, or alcohol reduction for the secondary prevention of gout. A prospective study of primary gout involving 47,150 men followed over 12 years noted a relative risk (RR) of gout 1.41 (95% confidence interval [CI], 1.07–1.86) in the highest quintile of meat eaters, a RR of 1.51 (95% CI, 1.17–1.95) in the highest quintile of seafood eaters, and an inverse relationship of dairy intake with gout risk.8 Thiazide diuretics appear to increase the likelihood of a gout diagnosis and if used, could be discontinued, although no studies have investigated this intervention. Most of the gout studies were performed in the 1960s using simple cohort designs and limited statistical analysis; some used combinations of medications and variable dosing. Only allopurinol appears effective in resorbing tophi5 and may have greater utility for patients with severe tophaceous gout, in those intolerant to uricosurics, in gross overproduction of uric acid, for patients with uric acid stones, or for those with renal impairment.
Recommendations from others
An expert panel, recruited by the Agency for Healthcare Research and Quality, recently published a summary combining evidence and expert opinion, which suggested that colchicine is a good prophylactic therapy and that uric acid lowering drugs (allopurinol, probenecid, and sulfinpyrazone) are effective in decreasing attack frequency in those with more than 2 attacks per year.9 Weight loss and alcohol reduction were also encouraged. A Cochrane review of this topic is scheduled for completion in 2004.
Prophylactic therapy is recommended for frequent attacks
Thuy Hanh Trinh, MD
Baylor College of Medicine, Houston, Tex
Long-term therapy is recommended when frequent gouty attacks occur. Care is warranted in the use of colchicine with erythromycin, simvastatin, and cyclosporine, since these drugs modify the excretion of colchicine, which may lead to toxic doses.10 Uric acid–lowering agents, such as allopurinol and probenecid, should be avoided in acute attacks of gout, due to potential worsening of inflammation.
Nonadherence with long-term prophylactic therapy for gout can lead to acute attacks, but patients who adhere to prophylactic therapy can still experience occasional acute breakthroughs of gout. The Cochrane review in progress may shed more insight into the prevention of acute gouty inflammation..
1. Paulus HE, Schlosstein LH, Godfrey RG, Klinenberg JR, Bluestone R. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974;17:609-614.
2. Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout. Prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med 1961;55:179-192.
3. Gutman AB. Treatment of primary gout: the present status. Arthritis Rheum 1965;8:911-920.
4. Rundles RW, Metz EN, Silberman HR. Allopurinol in the treatment of gout. Ann Int Med 1966;64:229-258.
5. Kuzell WC, Seebach LM, Glover RP, Jackman AE. Treatment of gout with allopurinol and sulphinpyrazone in combination and with allopurinol alone. Ann Rheum Dis 1966;25:634-642.
6. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study. Ann Rheum Dis 2000;59:539-543.
7. Gaines LM, Shulman LE. The failure of uricosuric drugs to reduce the attack rate in primary non-tophaceous gout. Arthritis Rheum 1969;12:663.-
8. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093-1103.
9. Mikuls TR, MacLean CH, Olivieri J, et al. Quality of care indicators for gout management. Arthritis Rheum 2004;50:937-943.
10. Terkeltaub R. Clinical practice. Gout. N Engl J Med 2003;349:1647-1655.
Colchicine (strength of recommendation [SOR]: B, based on 1 double-blind crossover study), allopurinol (SOR: B, based on 2 cohort studies), and weight loss (SOR: B, based on 1 small cohort study) have been shown to reduce symptomatic recurrences of gout, although the data to support their use is limited. Some evidence suggests that despite their serum uric acid–lowering effects, uricosurics (such as probenecid) fail to reduce gout attacks (SOR: B, based on 2 cohort studies). We were unable to find any double-blind, placebo-controlled long-term outcome studies addressing this problem.
Evidence summary
The majority of gout sufferers are uric acid undersecretors rather than overproducers; however, many patients will have a combination of these 2 processes, as well as caloric or purine overindulgence. Efforts to limit the frequency and intensity of gout attacks have focused on reducing the uric acid load or reducing the inflammatory response to intra-articular crystal deposition. Pharmacologic therapies include 1) uricosurics, such as probenecid, sulfinpyrazone and benzbromarone (used mostly in Europe), which increase the renal clearance of uric acid, 2) xanthine oxidase inhibitors such as allopurinol, which limit the formation of uric acid to yield a more water soluble chemical, and 3) anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. Obesity and insulin resistance are associated with elevated uric acid, suggesting that weight loss may also help reduce episodes of gout.
A double-blinded crossover study of 38 veteran men with recurrent gout found that the addition of daily colchicine to uricosurics reduced the frequency of attacks by nearly two thirds in 6 months of follow-up.1 A cohort study of 208 men with confirmed gout who used either daily colchicine alone or colchicine with uricosurics for 2 to 10 years found marked improvements in attack frequency in both groups, yet there was no difference between the intervention groups.2 An additional study followed 734 patients (including some of the subjects in the first cohort study) and reported similar outcomes.3
Allopurinol was studied in 46 patients using prophylactic colchicine with an average follow-up of 12 months.4 Attack rates were unchanged for the first several weeks followed by a decline in the attack rate and a regression of tophi. When allopurinol was added to uricosurics in 48 patients, tophi were reduced.5
An average weight loss of 7.7 kg had a beneficial effect on serum uric acid levels and gout attack rates in 13 nondiabetic men, who were placed on a carefully controlled 1600-calorie diet with 40% of calories from complex carbohydrates.6
In a small study, the addition of uricosurics did not reduce the gout attack rate in 14 patients with nontophaceous gout.7 Patients were followed over 12 to 15 months in a crossover study of colchicine and placebo versus colchicine and sulfinpyrazone. Although this study had limited power, a larger cohort study had similar findings over a longer follow-up period.3
We were unable to find any applicable studies of daily NSAID use, dietary purine control, or alcohol reduction for the secondary prevention of gout. A prospective study of primary gout involving 47,150 men followed over 12 years noted a relative risk (RR) of gout 1.41 (95% confidence interval [CI], 1.07–1.86) in the highest quintile of meat eaters, a RR of 1.51 (95% CI, 1.17–1.95) in the highest quintile of seafood eaters, and an inverse relationship of dairy intake with gout risk.8 Thiazide diuretics appear to increase the likelihood of a gout diagnosis and if used, could be discontinued, although no studies have investigated this intervention. Most of the gout studies were performed in the 1960s using simple cohort designs and limited statistical analysis; some used combinations of medications and variable dosing. Only allopurinol appears effective in resorbing tophi5 and may have greater utility for patients with severe tophaceous gout, in those intolerant to uricosurics, in gross overproduction of uric acid, for patients with uric acid stones, or for those with renal impairment.
Recommendations from others
An expert panel, recruited by the Agency for Healthcare Research and Quality, recently published a summary combining evidence and expert opinion, which suggested that colchicine is a good prophylactic therapy and that uric acid lowering drugs (allopurinol, probenecid, and sulfinpyrazone) are effective in decreasing attack frequency in those with more than 2 attacks per year.9 Weight loss and alcohol reduction were also encouraged. A Cochrane review of this topic is scheduled for completion in 2004.
Prophylactic therapy is recommended for frequent attacks
Thuy Hanh Trinh, MD
Baylor College of Medicine, Houston, Tex
Long-term therapy is recommended when frequent gouty attacks occur. Care is warranted in the use of colchicine with erythromycin, simvastatin, and cyclosporine, since these drugs modify the excretion of colchicine, which may lead to toxic doses.10 Uric acid–lowering agents, such as allopurinol and probenecid, should be avoided in acute attacks of gout, due to potential worsening of inflammation.
Nonadherence with long-term prophylactic therapy for gout can lead to acute attacks, but patients who adhere to prophylactic therapy can still experience occasional acute breakthroughs of gout. The Cochrane review in progress may shed more insight into the prevention of acute gouty inflammation..
Colchicine (strength of recommendation [SOR]: B, based on 1 double-blind crossover study), allopurinol (SOR: B, based on 2 cohort studies), and weight loss (SOR: B, based on 1 small cohort study) have been shown to reduce symptomatic recurrences of gout, although the data to support their use is limited. Some evidence suggests that despite their serum uric acid–lowering effects, uricosurics (such as probenecid) fail to reduce gout attacks (SOR: B, based on 2 cohort studies). We were unable to find any double-blind, placebo-controlled long-term outcome studies addressing this problem.
Evidence summary
The majority of gout sufferers are uric acid undersecretors rather than overproducers; however, many patients will have a combination of these 2 processes, as well as caloric or purine overindulgence. Efforts to limit the frequency and intensity of gout attacks have focused on reducing the uric acid load or reducing the inflammatory response to intra-articular crystal deposition. Pharmacologic therapies include 1) uricosurics, such as probenecid, sulfinpyrazone and benzbromarone (used mostly in Europe), which increase the renal clearance of uric acid, 2) xanthine oxidase inhibitors such as allopurinol, which limit the formation of uric acid to yield a more water soluble chemical, and 3) anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. Obesity and insulin resistance are associated with elevated uric acid, suggesting that weight loss may also help reduce episodes of gout.
A double-blinded crossover study of 38 veteran men with recurrent gout found that the addition of daily colchicine to uricosurics reduced the frequency of attacks by nearly two thirds in 6 months of follow-up.1 A cohort study of 208 men with confirmed gout who used either daily colchicine alone or colchicine with uricosurics for 2 to 10 years found marked improvements in attack frequency in both groups, yet there was no difference between the intervention groups.2 An additional study followed 734 patients (including some of the subjects in the first cohort study) and reported similar outcomes.3
Allopurinol was studied in 46 patients using prophylactic colchicine with an average follow-up of 12 months.4 Attack rates were unchanged for the first several weeks followed by a decline in the attack rate and a regression of tophi. When allopurinol was added to uricosurics in 48 patients, tophi were reduced.5
An average weight loss of 7.7 kg had a beneficial effect on serum uric acid levels and gout attack rates in 13 nondiabetic men, who were placed on a carefully controlled 1600-calorie diet with 40% of calories from complex carbohydrates.6
In a small study, the addition of uricosurics did not reduce the gout attack rate in 14 patients with nontophaceous gout.7 Patients were followed over 12 to 15 months in a crossover study of colchicine and placebo versus colchicine and sulfinpyrazone. Although this study had limited power, a larger cohort study had similar findings over a longer follow-up period.3
We were unable to find any applicable studies of daily NSAID use, dietary purine control, or alcohol reduction for the secondary prevention of gout. A prospective study of primary gout involving 47,150 men followed over 12 years noted a relative risk (RR) of gout 1.41 (95% confidence interval [CI], 1.07–1.86) in the highest quintile of meat eaters, a RR of 1.51 (95% CI, 1.17–1.95) in the highest quintile of seafood eaters, and an inverse relationship of dairy intake with gout risk.8 Thiazide diuretics appear to increase the likelihood of a gout diagnosis and if used, could be discontinued, although no studies have investigated this intervention. Most of the gout studies were performed in the 1960s using simple cohort designs and limited statistical analysis; some used combinations of medications and variable dosing. Only allopurinol appears effective in resorbing tophi5 and may have greater utility for patients with severe tophaceous gout, in those intolerant to uricosurics, in gross overproduction of uric acid, for patients with uric acid stones, or for those with renal impairment.
Recommendations from others
An expert panel, recruited by the Agency for Healthcare Research and Quality, recently published a summary combining evidence and expert opinion, which suggested that colchicine is a good prophylactic therapy and that uric acid lowering drugs (allopurinol, probenecid, and sulfinpyrazone) are effective in decreasing attack frequency in those with more than 2 attacks per year.9 Weight loss and alcohol reduction were also encouraged. A Cochrane review of this topic is scheduled for completion in 2004.
Prophylactic therapy is recommended for frequent attacks
Thuy Hanh Trinh, MD
Baylor College of Medicine, Houston, Tex
Long-term therapy is recommended when frequent gouty attacks occur. Care is warranted in the use of colchicine with erythromycin, simvastatin, and cyclosporine, since these drugs modify the excretion of colchicine, which may lead to toxic doses.10 Uric acid–lowering agents, such as allopurinol and probenecid, should be avoided in acute attacks of gout, due to potential worsening of inflammation.
Nonadherence with long-term prophylactic therapy for gout can lead to acute attacks, but patients who adhere to prophylactic therapy can still experience occasional acute breakthroughs of gout. The Cochrane review in progress may shed more insight into the prevention of acute gouty inflammation..
1. Paulus HE, Schlosstein LH, Godfrey RG, Klinenberg JR, Bluestone R. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974;17:609-614.
2. Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout. Prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med 1961;55:179-192.
3. Gutman AB. Treatment of primary gout: the present status. Arthritis Rheum 1965;8:911-920.
4. Rundles RW, Metz EN, Silberman HR. Allopurinol in the treatment of gout. Ann Int Med 1966;64:229-258.
5. Kuzell WC, Seebach LM, Glover RP, Jackman AE. Treatment of gout with allopurinol and sulphinpyrazone in combination and with allopurinol alone. Ann Rheum Dis 1966;25:634-642.
6. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study. Ann Rheum Dis 2000;59:539-543.
7. Gaines LM, Shulman LE. The failure of uricosuric drugs to reduce the attack rate in primary non-tophaceous gout. Arthritis Rheum 1969;12:663.-
8. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093-1103.
9. Mikuls TR, MacLean CH, Olivieri J, et al. Quality of care indicators for gout management. Arthritis Rheum 2004;50:937-943.
10. Terkeltaub R. Clinical practice. Gout. N Engl J Med 2003;349:1647-1655.
1. Paulus HE, Schlosstein LH, Godfrey RG, Klinenberg JR, Bluestone R. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974;17:609-614.
2. Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout. Prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med 1961;55:179-192.
3. Gutman AB. Treatment of primary gout: the present status. Arthritis Rheum 1965;8:911-920.
4. Rundles RW, Metz EN, Silberman HR. Allopurinol in the treatment of gout. Ann Int Med 1966;64:229-258.
5. Kuzell WC, Seebach LM, Glover RP, Jackman AE. Treatment of gout with allopurinol and sulphinpyrazone in combination and with allopurinol alone. Ann Rheum Dis 1966;25:634-642.
6. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study. Ann Rheum Dis 2000;59:539-543.
7. Gaines LM, Shulman LE. The failure of uricosuric drugs to reduce the attack rate in primary non-tophaceous gout. Arthritis Rheum 1969;12:663.-
8. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093-1103.
9. Mikuls TR, MacLean CH, Olivieri J, et al. Quality of care indicators for gout management. Arthritis Rheum 2004;50:937-943.
10. Terkeltaub R. Clinical practice. Gout. N Engl J Med 2003;349:1647-1655.
Evidence-based answers from the Family Physicians Inquiries Network